Hydrogen exhibits the potential to treat Alzheimer’s disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic (3×Tg) Alzheimer’s disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer’s disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer’s disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China (approval No. AEWC-20140615-002) on June 15, 2014.